Pharmaceutical applications for methanediphosphonate derivative

Abstract

The present invention relates to a methanediphosphonate derivative, its manufacturing process, and pharmaceutical applications, that is represented with the following formula: ##STR1## wherein, D is either sulfur, oxygen, NH, alkyl-substituted N, CH.sub.2, or SCH.sub.2, X represents an alkyl group, alkyl group having a hetero atom as a substitution group, an aryl group or an acyl group, m represents an integer of 1 to 5, and R.sup.1, R.sup.2, R.sup.3 and R.sup.4 independently represent hydrogen, alkyl groups having 1 to carbon atoms or pharmaceutically allowable cations. .function.The compounds of the present invention have excellent IL-1 inhibitory action, antioxidation action and bone resorption inhibitory action, and are useful as antiinflammatory agents, antirheumatic agents, bone metabolic disease drugs, autoimmune disease drugs, or osteoporosis drugs.

Claims

1. A method of treating diseases selected from the group consisting of rheumatism and bone metabolic disease, and for inhibiting patient physiological conditions selected from the group consisting of inflammation, interleukin-1 production, interleukin-1-induced cellular response, active oxygen production in neutrophils and bone resorption, comprising administering an effective amount of a methanediphosphonate derivative represented by formula (I): ##STR44## where, X represents H, a straight chain or branched chain alkyl group having 1 to 8 carbon atoms that is either unsubstituted or substituted, an aryl group, or an acyl group,

Y represents a halogen atom, nitrile group, nitro group, alkyl group, alkoxy group, trifluoromethyl group, hydroxyl group, acyloxy group, acylamino group, acyl group, alkenyl group, aryl group, cycloalkyl group, COOH group, COO-alkyl group, ##STR45## (wherein Z.sup.1 and Z.sup.2 represent, independently of each other, hydrogen atoms or alkyl groups, or Z.sup.1 and Z.sup.2 may form a ring composed of carbon atoms or a ring composed of carbon atoms containing hetero atoms) or ##STR46## (wherein Z.sup.1 and Z.sup.2 represent the same groups as indicated above, and Z.sup.3 represents oxygen or sulfur),

m represents an integer of 1 to 5, n represents an integer of 0 to 4 (provided that m+n is 5 or less), the m number of XS and the n number of Y may be either identical or different, respectively,

.. represents a double bond or a single bond,

A is --(CH.sub.2)a-(D)b-(CH.sub.2)c- (D is sulfur, oxygen, NH, alkyl-substituted N or CH.sub.2, a and c are integers of 0 to 10, and b is 0 or 1), or --(CH.dbd.CH)d-CH.dbd. (d is an integer of 0 to 2, and B does not exist in the case when A represents --(CH.dbd.CH) d-CH.dbd.,

B represents a hydrogen atom, an alkyl group, amino group, monoalkylamino group, dialkylamino group, acylamino group, hydroxyl group, an alkoxy group, trialkylsiloxy group or acyloxy group, and

R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are identical or different, and are hydrogen atoms, straight or branched chain alkyl groups having 1 to 7 carbon atoms or pharmaceutically acceptable cations.

2. The method defined in claim 1 wherein said effective amount is about 0.1 mg-5.0 g once or several times per one day to seven days.